Open AccessDepletion and activation of mucosal CD4 T cells in HIV infected women with HPV-associated lesions of the cervix uteri
Author(s) -
Wilbert Mbuya,
Ruby Mcharo,
Jacklina Mhizde,
Jonathan Mnkai,
Anifrid Mahenge,
Maria Mwakatima,
Wolfram Mwalongo,
Nhamo Chiwerengo,
Michael Hölscher,
Tessa Lennemann,
Elmar Saathoff,
Liset Torres,
Arne Kroidl,
Christof Geldmacher,
Kathrin Held,
Mkunde Chachage
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0240154
Subject(s) - cd8 , cervix , medicine , hpv infection , flow cytometry , immunology , coinfection , human immunodeficiency virus (hiv) , cervical cancer , immune system , cancer
Background The burden of HPV-associated premalignant and malignant cervical lesions remains high in HIV+ women even under ART treatment. In order to identify possible underlying pathophysiologic mechanisms, we studied activation and HIV co-receptor expression in cervical T-cell populations in relation to HIV, HPV and cervical lesion status. Methods Cervical cytobrush (n = 468: 253 HIV- and 215 HIV+; 71% on ART) and blood (in a subset of 39 women) was collected from women in Mbeya, Tanzania. Clinical data on HIV and HPV infection, as well as ART status was collected. T cell populations were characterized using multiparametric flow cytometry-based on their expression of markers for cellular activation (HLA-DR), and memory (CD45RO), as well as HIV co-receptors (CCR5, α 4 β 7 ). Results Cervical and blood T cells differed significantly, with higher frequencies of T cells expressing CD45RO, as well as the HIV co-receptors CCR5 and α 4 β 7 in the cervical mucosa. The skewed CD4/CD8 T cell ratio in blood of HIV+ women was mirrored in the cervical mucosa and HPV co-infection was linked to lower levels of mucosal CD4 T cells in HIV+ women (%median: 22 vs 32; p = 0.04). In addition, HIV and HPV infection, and especially HPV-associated cervical lesions were linked to significantly higher frequencies of HLA-DR+ CD4 and CD8 T cells (p-values < 0.05). Interestingly, HPV infection did not significantly alter frequencies of CCR5+ or α 4 β 7 + CD4 T cells. Conclusion The increased proportion of activated cervical T cells associated with HPV and HIV infection, as well as HPV-associated lesions, together with the HIV-induced depletion of cervical CD4 T cells, may increase the risk for HPV infection, associated premalignant lesions and cancer in HIV+ women. Further, high levels of activated CD4 T cells associated with HPV and HPV-associated lesions could contribute to a higher susceptibility to HIV in HPV infected women.